NM_139172.3:c.187C>G

Variant names:

• chr19-55377685-C-G
• rs746356643
• NM_139172.3:c.187C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_139172.3(TMEM190):​c.187C>G​(p.Arg63Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R63C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 30)
• Consequence: TMEM190 NM_139172.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.200
• Publications: 0 publications found

Genes affected

TMEM190 (HGNC:29632): (transmembrane protein 190) Predicted to enable protein self-association. Predicted to be involved in hematopoietic progenitor cell differentiation. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000269275 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_139172.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM190	NM_139172.3	MANE Select	c.187C>G	p.Arg63Gly	missense	Exon 3 of 5	NP_631911.1	Q8WZ59

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM190	ENST00000291934.4	TSL:1 MANE Select	c.187C>G	p.Arg63Gly	missense	Exon 3 of 5	ENSP00000291934.3	Q8WZ59
	TMEM190	ENST00000914204.1		c.95-117C>G		intron	N/A	ENSP00000584263.1
	ENSG00000269275	ENST00000595064.1	TSL:6	n.441G>C		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.55
BayesDel_addAF	Benign	-0.017	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.21	T
Eigen	Benign	0.048
Eigen_PC	Benign	-0.019
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.071	D
MetaRNN	Uncertain	0.58	D
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.0	L
PhyloP100		0.20
PrimateAI	Uncertain	0.61	T
PROVEAN	Uncertain	-3.7	D
REVEL	Benign	0.16
Sift	Uncertain	0.025	D
Sift4G	Uncertain	0.016	D
Polyphen		0.99	D
Vest4		0.60
MutPred		0.40		Loss of sheet (P = 0.0457)
MVP		0.29
MPC		0.93
ClinPred		0.63	D
GERP RS		2.8
Varity_R		0.28
gMVP		0.69
Mutation Taster		=74/26	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs746356643; hg19: chr19-55889053;